The goals of this project are an understanding of the permeability of rickettsiae and a knowledge of their mode of penetration into their host cell. The transport systems evolved by obligatory intracellular parasites should reflect their adaptation to the unique demands and opportunities of an existence within the cytoplasm of their host. The transport of glutamate, nucleotides, sugars, sugar-phosphates and ions are of interest and will be studied by millipore filtration, analysis of chemical and isotope pools and "micro-space" measurements. The biochemistry of the rickettsiae will be correlated with the availability of transport systems for the substrates of their enzymatic activities. A comparison of rickettsial transport systems, metabolic pathways and cell envelope with free-living bacteria and mitochondria will be made. An understanding of the mechanism by which rickettsiae enter their host cell will provide insight into the invasive properties of many parasitic cells. The penetration study will utilize both tissue culture cells and erythrocytes. The latter may provide an excellent model system, if rickettsial hemolysis is an abortive attempt to parasitize the erythrocyte. The role of rickettsial and host metabolism, phagocytosis and the control of the lysosomal response, fusion and membrane resealing will be evaluated. Both biochemical and scanning and transmission electron microscopic techniques will be utilized in this investigation. BIBLIOGRAPHIC REFERENCES: Winkler, H. H. Rickettsial permeability: An ADP-ATP transport system. J. Biol. Chem. 251:389-396. 1976. Ramm, L. E. and H. H. Winkler. Identification of cholesterol in the receptor site for rickettsiae on sheep erythrocyte membranes. Infection and Immunity 13:120-126. 1976.